INHIBIN AND ACTIVIN HAVE ANTAGONISTIC PARACRINE EFFECTS ON GONADAL STEROIDOGENESIS DURING THE DEVELOPMENT OF THE CHICKEN-EMBRYO

Primary cultures of gonadal cells from chicken embryos were used to ex plore the paracrine role of inhibin and activin during gonadal develop ment. Fetal testicular and ovarian cells secreted high amounts of immu noactive inhibin. FSH caused a dose-related increase of cAMP and immun oactive inhibin concentrations in testicular cell cultures. Postrecept or signalling through the protein kinase A (PKA) pathway was confirmed by additional experiments with 8-bromo-cAMP, 3-isobutyl-1-methyl-xant hine (MIX), prostaglandins, forskolin, and choleratoxin. The relative ability of these agonists to stimulate cAMP production did not always correlate with their ability to stimulate inhibin secretion. Experimen ts with phorbol 12-myristate 13-acetate suggested that the regulation of immunoactive inhibin secretion also involves the protein kinase C ( PKC) pathway. In addition, it was shown that recombinant human (rh)-in hibin increases the conversion of pregnenolone to androgens whereas rh -activin has the opposite effect. Recombinant human follistatin, an ac tivin-binding protein, antagonized the actions of rh-activin and to a lesser extent those of rh-inhibin. In conclusion, these results show t hat during the development of the chicken embryo, gonadal inhibin secr etion may be regulated by hormones and by local factors such as prosta glandins. Cross talk between the PKA and PKC pathways may be involved in this regulation. Recombinant human inhibin and rh-activin may have antagonistic roles in the paracrine control of gonadal steroidogenesis .